title: Ethanol consumption increases endothelin-1 expression and reactivity in the rat cavernosal smooth muscle.
abstract: OBJECTIVE
  We investigated the effects of chronic ethanol consumption on the cavernosal smooth muscle (CSM) reactivity to endothelin-1 (ET-1) and the expression of ET system components in this tissue.
  
  
  METHODS
  Male Wistar rats were treated with heavy dose of ethanol (20% v/v) for 6 weeks. Reactivity experiments were performed in the isolated rat CSM. Plasma and CSM nitrate generation and also superoxide anion generation in rat CSM were measured by chemiluminescence. Protein and mRNA levels of pre-pro-ET-1, endothelin-converting enzyme-1 (ECE-1), ETA and ETB receptors, eNOS, nNOS and iNOS were assessed by western immunoblotting and quantitative real-time polymerase chain reaction, respectively.
  
  
  RESULTS
  Chronic ethanol consumption increased plasma ET-1 levels and the contractile response induced by this peptide in the isolated CSM. The relaxation induced by acetylcholine, but not IRL1620, a selective ETB receptor agonist, was reduced in CSM from ethanol-treated rats. BQ123, a selective ETA receptor antagonist, produced a rightward displacement of the ET-1 concentration-response curves in CSM from control, but not ethanol-treated rats. Reduced levels of nitrate were found in the plasma and CSM from ethanol-treated rats. Ethanol consumption increased superoxide anion generation in the rat CSM. The mRNA levels of pre-pro-ET-1, ECE-1, ETA and ETB receptors, eNOS, nNOS and iNOS were not altered by ethanol consumption. Protein levels of ET-1, ETA receptor and iNOS were higher in the CSM from rats chronically treated with ethanol.
  
  
  CONCLUSIONS
  The major findings of the present study are that heavy ethanol consumption increases plasma ET-1 levels and the contraction induced by the peptide in the CSM. Increased CSM reactivity to ET-1 and altered protein levels of ET-1 and ETA receptors could play a role in the pathogenesis of erectile dysfunction associated with chronic ethanol consumption.
authors.affiliation: Corresponding author: Universidade de São Paulo, Escola de Enfermagem de Ribeirão Preto, Laboratório de Farmacologia, Avenida Bandeirantes 3900, CEP 14040-902, Ribeirão Preto, SP, Brazil. crtirapelli@eerp.usp.br.
authors.forename: Letícia N
authors.initials: LN
authors.lastname: Leite
authors.forename: Riccardo
authors.initials: R
authors.lastname: Lacchini
authors.forename: Evelin C
authors.initials: EC
authors.lastname: Carnio
authors.forename: Regina H
authors.initials: RH
authors.lastname: Queiroz
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Tanus-Santos
authors.forename: Ana M
authors.initials: AM
authors.lastname: de Oliveira
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Tirapelli
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000097:blood; D000072396:Endothelin-Converting Enzymes; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D049449:Luminescence; D008297:Male; D008666:Metalloendopeptidases / Q000096:biosynthesis; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010413:Penis / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D044022:Receptor, Endothelin A / Q000096:biosynthesis; D044023:Receptor, Endothelin B / Q000096:biosynthesis; D013481:Superoxides / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D019332:Endothelin-1; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013481:Superoxides; D009569:Nitric Oxide; D000431:Ethanol; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes